1. Field of the Invention
The present invention relates to a method and package for storing a pressurized container containing a drug.
2. Description of the Background Art
For environmental reasons, there has been a move to replace chlorofluorocarbons (CFCs) (also simply known as xe2x80x9cfluorocarbonsxe2x80x9d) such as P11, P114 and P12 with hydrofluoroalkane propellants such as HFA-134a and HFA-227. When these hydrofluoroalkane propellants are used as a propellant in a pressurized drug delivery system, various technical problems can occur with various drug formulations. Also, it is necessary to modify the construction of metered dose inhalers for optimum stability and aerosol formation.
One storing mechanism for a metered dose inhaler (MDI) uses a plastic tube which has a resealable lid to close the tube. The resealable lid for this tube employs a desiccant to absorb moisture present in the tube.
Such plastic tubes typically increase manufacturing cost and require complex and/or expensive manufacturing processes. Such tubes are frequently bulky in that they require a significant amount of storage space relative to the size of the container disposed within the plastic tube.
It is well established that non-CFC propellants, especially HFC 134a, have a much greater water solubility than the CFC propellants traditionally used in MDI""s. The maximum water solubility in HFC 134a is about 2200 ppm whereas for CFC 11, 12 and 114, the maximum water solubilities are about 130 ppm. (See Pischtiak, A. (1999) xe2x80x9cSolvay Fluor and Derivate Chemical Data Sheet for CFC and HFC Propellants.xe2x80x9d)
This maximum solubility may be further increased if cosolvents such as ethanol are used in the formulation. The mechanism of moisture transport into HFC MDI""s has been discussed by Williams, G. and Tcherevatchenkoff, A. (1999) xe2x80x9cMoisture Transport Into CFC-Free MDI""s,xe2x80x9d Respiratory Drug Delivery VI, Hilton Head, S.C., USA.
They concluded that moisture transport is influenced by the elastomeric nature of the valve gaskets as well as the type of HFA formulation and storage conditions employed. It may be appropriate, under certain circumstances to control the ingress of moisture into HFC based MDI""s. A good example of this would be with a hygroscopic drug substance. Hence, prevention of moisture ingress is the subject of this invention whereby a series of secondary packaging embodiments demonstrate advantageously reducing moisture ingress.
Accordingly, a need in the art exists for a method and package for storing a pressurized container filled with a propellant and a drug which substantially prevents ingression of water vapor and particulate matter into the storage package while permitting egression of the propellant to increase shelf life and performance of the drug and the propellant. Furthermore, a need exists in the art to provide a method and package for storing a pressurized container filled with a drug and a propellant which is cost effective and which does not require complex manufacturing processes and which in turn efficiently envelopes the container to maximize available storage space.
It is a primary object of the present invention to provide a method and package for storing a pressurized container, where the pressurized container is filled with a drug and a propellant and where the method and package substantially prevent ingression of water vapor and particulate matter into the package while permitting egression of the propellant whereby shelf life of the drug is prolonged and performance of the drug and the propellant are maintained or increased.
It is a further object of the present invention to provide a method and package for storing a pressurized container filled with a drug and a propellant where the method and package substantially absorb residual moisture in the package enclosing the pressurized container that is sometimes present on the outer surface of the pressurized container prior to sealing pressurized container within the package.
Another object of the present invention is to provide a method and package for storing a pressurized container including a drug and a propellant which substantially reduces manufacturing costs while substantially reducing the complexity of the manufacturing process of the package.
Another object of the present invention is to provide a method and package for storing a pressurized container having a drug and a propellant which is easily opened and readily disposable.
It is a further object of the present invention to provide a method and package for storing a pressurized container having a drug and a propellant, whereby the propellant preferably meets governmental guidelines which prohibit the use of CFCs.
Another object of the present invention is to provide a method and package for storing a pressurized container which includes a drug and a propellant that does not require complex mechanical devices to envelope or enclose the pressurized container while substantially reducing the amount of storage space needed for the pressurized container where the package substantially conforms to the shape of the pressurized container. The package is amorphous in shape due to the flexible materials from which it is made.
Another object of the present invention is to provide a method and package which form an enclosed volume that stores a pressurized container in a controlled environment where the pressurized container is isolated from harmful environmental conditions such as humidity, dust, light, and water vapor and other particulate matter.
Another object of the present invention is to provide and article of manufacture comprising an integral aerosol dispensing apparatus, a drug formulation, and a flexible package. It is further an object of the present invention to provide a drug formulation and carrier with packaging material having labeling and information relating to the composition contained therein and printed thereon. Additionally, a further object of the invention is to provide an article of manufacture having a brochure, report, notice, pamphlet, or leaflet containing product information.
These and other objects of the present invention are fulfilled by providing a container storage system comprising: a drug formulation comprising a mixture of a drug and a propellant; a pressurized container filled with the drug formulation at a predetermined pressure; and a flexible package for wrapping and sealing the pressurized container providing an enclosed volume in which the pressurized container is disposed, the flexible package being impermeable to water vapor and permeable to the propellant, the flexible package substantially preventing ingression of water vapor and particulate matter into the enclosed volume while permitting egression of the propellant.
In addition, these and other objects of the present invention are also accomplished by providing a method of storing a container comprising the steps of: providing a flexible package material, which is impermeable to water vapor and permeable to a propellant; filling a container with a drug formulation comprising a drug and the propellant at a predetermined pressure; wrapping the container with the flexible package material to form an enclosed volume in which the container is disposed therein; and sealing the flexible package which in turn closes said enclosed volume, the flexible package substantially preventing ingression of water vapor and particulate matter into the enclosed volume while permitting egression of the propellant from the enclosed volume.
Moreover, these and other objects of the present invention are fulfilled by a packaged metered dose inhaler comprising: an MDI comprising a container and a drug metering valve, a pressurized drug formulation in the container comprising a propellant and a drug dispersed or dissolved in the propellant; and an overwrap of flexible material enclosing said MDI, the overwrap being made of a moisture impermeable material.
Also, these and other objects of present invention are accomplished by providing an article of manufacture comprising: an aerosol dispensing apparatus for dispensing metered amounts of fluid material from a reservoir, the apparatus comprising a container defining a reservoir, a dispensing valve; a drug formulation located within the aerosol dispensing apparatus comprising a safe and effective medicament and a pharmaceutically acceptable propellant; and a flexible package for wrapping and sealing the container providing an enclosed volume in which said pressurized container is disposed, the flexible package being substantially impermeable to water vapor and permeable to the propellant, the flexible package substantially preventing ingression of water vapor and particulate matter into the enclosed volume while permitting egression of the propellant.
These and other objects of the present invention are also accomplished by providing a method of improving a product performance comprising the steps of: providing a flexible package material made of at least one heat sealable layer, at least one layer of a metal foil, and a protective layer; the flexible package material being impermeable to water vapor and permeable to a propellant; filling a container with a drug formulation comprising a drug and the propellant at a predetermined pressure; wrapping the container with the flexible package material to form an enclosed volume in which the container is disposed therein; and sealing the flexible package which in turn closes the enclosed volume, the flexible package substantially preventing ingression of water vapor and particulate matter into the enclosed volume while permitting egression of the propellant from the enclosed volume.
Another aspect of the invention includes a desiccant-containing, substantially moisture impermeable film that has been heat-shrinked onto portions of the metered dose inhaler. By xe2x80x9csubstantially moisture impermeablexe2x80x9d it is meant that no more than insignificant or trace amounts of moisture may pass through the film. This invention is directed to an apparatus comprising a drug formulation comprising a mixture of at least a drug and an HFA propellant, a fluid dispensing device including a pressurized container filled with said drug formulation, and a substantially moisture-impermeable polymeric film heat-shrinked onto at least a portion of the exterior of the fluid dispensing device, wherein the polymeric film comprises a first moisture absorbing material. Preferably, the drug is albuterol sulfate and the propellant is HFA 134a. The fluid dispensing device may further include a valve having a stem. Preferably the film is heat-shrinked onto the pressurized container, the valve, and the region defined by the exterior interface of the valve and stem. Alternatively, the film may be heat-shrinked onto a portion of the pressurized container and a portion of the valve. The apparatus may further include a second moisture absorbing material located within the pressurized container. The first and second moisture absorbing material may be a desiccant such as nylon, silica gel, zeolite, alumina, bauxite, anhydrous calcium sulphate, activated bentonite clay, water absorbing clay, molecular sieve or combinations thereof. The second desiccant may be contained within a sachet constructed from nylon or loose within the pressurized container. The sachet may be fixedly attached to the pressurized container. The second desiccant may be in the form of granules or beads suitably large in size to avoid clogging a valve in the metered dose inhaler.
The polymeric film of the heat shrink wrap may be constructed from one or more polymeric layers. Preferably, the one or more polymeric layers of the polymeric film are each constructed from polyvinylchloride, polyvinylidenechloride, polypropylene, oriented polypropylene, polyethylene, ACLAR(copyright) or BAREX(copyright). Preferably, individual or a combination of polymeric layers are oriented or otherwise modified so as to provide a customized shrinking. For example, the oriented polypropylene layer may be employed in such a manner so as to provide predominately greater shrinking around the valve/cannister interface, at the valve/stem interface and around the rest of the cannister (as opposed to along the length of the MDI) to provide enhanced sealing of the MDI to ambient moisture. Preferably, the polymeric film remains on the MDI during storage and throughout the useful life of the MDI to more advantageously (1) absorb any moisture located inside the MDI, and (2) seal off the MDI from ambient moisture. The polymeric film may further include one or more adhesive layers. The first moisture absorbing material may be a first desiccant. At least one of said polymeric layers may be impregnated, coated, treated or lined with said first desiccant. At least one of said adhesive layers may also be impregnated with the first desiccant. The desiccant may be incorporated with the polymeric or adhesive layer by conventional methods known in the art, such as by spray coating, blending prior to extrusion, or other suitable methods. Preferably, the substantially moisture-impermeable polymeric film is preformed or prefabricated. Such preforming or prefabrication may be performed by conventional methods such as by extruding the film layer, cutting to length and heat or chemical/mechanical sealing.
Further scope of applicability of the present invention will become apparent from the detailed description given hereinafter. However, it should be understood that the detailed description and specific examples, while indicating preferred embodiments of the invention, are given by way of illustration only, since various changes and modifications within the spirit and scope of the invention will become apparent to those skilled in the art from this detailed description.